Our long term objective is to elucidate neural mechanisms underlying the control of somatosensory transmission, with particular emphasis on nociceptive (pain) transmission in the superficial and deeper dorsal horn of the medulla (trigeminal nucleus caudalis). The hypothesis to be tested is that nociceptive transmission in the medullary dorsal horn is modulated by opiates, opioid-peptides and descending peptidergic (opioid) pathways. Specifically, descending peptidergic pathways from the perifornical region (PFX) and the paraventricular hypothalamic nucleus (PVN) modulate trigeminothalamic neurons projecting to different thalamic nuclei (ventrobasal complex, nucleus submedius).. Noradrenergic (LC, A7) and serotonergic (NRM) brainstem nuclei may mediate, in part, the descending modulation from PFX and PVN. The role of opiates and opioid peptides selective for different opioid receptors (mu, delta and kappa) will be investigated on the somatosensory and electrical stimuli-evoked responses of trigemino thalamic neurons in the superficial and the deeper dorsal horn of the medulla in anesthetized rats. Brain areas (PFX, PVN) will be stimulated electrically or chemically to identify their actions on the jaw opening reflex, and on neuronal activity in the medullary dorsal horn. The laminar and modality specificity of the modulatory influences will be investigated. Effects on innocuous cold-receptive neurons, low threshold mechanoreceptive neurons and on noxious versus the non-noxious stimuli evoked responses of multireceptive neurons will reveal if there is a selective antinociceptive effect. These studies will enhance our understanding of basic mechanisms related to pain perception and control, and shed light on the functional significance of multiple opioid peptides and opioid receptors in the medullary dorsal horn. This will eventually help to develop better and new treatments for the control of different clinical pain states.